The Global Architecture Shaping the Heterogeneity and Tissue-Dependency of the MHC Class I Immunopeptidome is Evolutionarily Conserved

Kubiniok, P.; Marcu, A.; Bichmann, L.; Kuchenbecker, L.; Schuster, H.; Hamelin, D.; Despault, J.; Kovalchik, K.; Wessling, L.; Kohlbacher, O.; Stevanovic, S.; Hans-Georg, R.; Neidert, M. C.; Sirois, I.; Caron, E.

doi:10.1101/2020.09.28.317750

bioRxiv · 10.1101/2020.09.28.317750

The Global Architecture Shaping the Heterogeneity and Tissue-Dependency of the MHC Class I Immunopeptidome is Evolutionarily Conserved

Kubiniok, P.·Marcu, A.·Bichmann, L.·Kuchenbecker, L.·Schuster, H.·Hamelin, D.·Despault, J.·Kovalchik, K.·Wessling, L.·Kohlbacher, O.·Stevanovic, S.·Hans-Georg, R.·Neidert, M. C.·Sirois, I.·Caron, E.

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Abstract

Understanding the molecular principles that govern the composition of the mammalian MHC-I immunopeptidome (MHC-Ii) across different primary tissues is fundamentally important to predict how T cell respond in different contexts in vivo. Here, we performed a global analysis of the mammalian MHC-Ii from 29 and 19 primary human and mouse tissues, respectively. First, we observed that different HLA-A, -B and -C allotypes do not contribute evenly to the global composition of the MHC-Ii across multiple human tissues. Second, we found that peptides that are presented in a tissue-dependent and -independent manner share very distinct properties. Third, we discovered that proteins that are evolutionarily hyperconserved represent the primary source of the MHC-Ii at the organism-wide scale. Finally, we uncovered new components of the antigen processing and presentation network that may drive the high level of heterogeneity of the MHC-Ii across different tissues in mammals. This study opens up new avenues toward a system-wide understanding of antigen presentation in vivo and may serve as ground work to understand tissue-dependent T cell responses in autoimmunity, infectious diseases and cancer.

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Kubiniok, P., Marcu, A., Bichmann, L., Kuchenbecker, L., Schuster, H., Hamelin, D., Despault, J., Kovalchik, K., Wessling, L., Kohlbacher, O., Stevanovic, S., Hans-Georg, R., Neidert, M. C., Sirois, I., Caron, E.. 2020-09-29. The Global Architecture Shaping the Heterogeneity and Tissue-Dependency of the MHC Class I Immunopeptidome is Evolutionarily Conserved. https://doi.org/10.1101/2020.09.28.317750

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